{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T05:34:24Z","timestamp":1777354464269,"version":"3.51.4"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Post-stroke infection (PSI), particularly pneumonia and urinary tract infection, is a common and serious complication after acute ischemic stroke (AIS). Current diagnostic biomarkers provide limited accuracy when used in isolation. This study aimed to evaluate the diagnostic value of circulating biomarkers and gut microbiota profiling, both individually and in combination, to predict PSI in AIS patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a prospective observational study at Prof. Dr. dr. Mahar Mardjono National Brain Center Hospital, Jakarta. A total of 80 AIS patients admitted within 24 h of onset were enrolled and followed for 7 days to assess PSI. Blood samples were analyzed for NMDAR, butyrate, TMAO, RANKL, iFABP, and LPS. Stool samples were collected for 16S rRNA sequencing. Diagnostic performance was evaluated using ROC curves, with AUC, sensitivity, and specificity calculated. Multivariate logistic regression models were constructed to assess independent predictors and combined diagnostic accuracy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PSI occurred in 37\/80 patients (46.3%). NMDAR showed the highest diagnostic performance (AUC 0.911; sensitivity 86.5%; specificity 90.7), followed by iFABP (AUC 0.894), LPS (AUC 0.896), RANKL (AUC 0.881), butyrate (AUC 0.866), and TMAO (AUC 0.865). Gut microbiota analysis revealed reduced evenness and dominance imbalance in infected patients, with enrichment of pathogenic taxa (\n                      <jats:italic>Escherichia coli, Salmonella enterica<\/jats:italic>\n                      ) and depletion of SCFA-producing commensals (\n                      <jats:italic>Faecalibacterium prausnitzii, Roseburia intestinalis<\/jats:italic>\n                      ). Multivariate models integrating microbiota features and biomarkers improved predictive accuracy compared with single-domain approaches.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Integrating circulating biomarkers with gut microbiota profiling significantly enhances early prediction of PSI in AIS. These findings highlight the role of the gut\u2013brain\u2013immune axis in post-stroke complications and support combined biomarker\u2013microbiota models for risk stratification and preventive strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2025.1702025","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T04:33:50Z","timestamp":1777350830000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic value of gut microbiota profiling and circulating biomarkers to predict post-stroke infection in acute ischemic stroke"],"prefix":"10.3389","volume":"12","author":[{"given":"Weny","family":"Rinawati","sequence":"first","affiliation":[{"name":"Doctoral Program in Medical Science, Faculty of Medicine, Universitas Airlangga","place":["Surabaya, Indonesia"]},{"name":"Laboratory and Blood Bank Unit, National Brain Center Hospital Mahar Mardjono","place":["Jakarta, Indonesia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aryati","family":"Aryati","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology, Faculty of Medicine, Universitas Airlangga","place":["Surabaya, Indonesia"]},{"name":"Dr. Soetomo General Academic Hospital","place":["Surabaya, Indonesia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdulloh","family":"Machin","sequence":"additional","affiliation":[{"name":"Dr. Soetomo General Academic Hospital","place":["Surabaya, Indonesia"]},{"name":"Department of Neurology, Faculty of Medicine, Universitas Airlangga","place":["Surabaya, Indonesia"]},{"name":"Airlangga University Hospital","place":["Surabaya, Indonesia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Kiechl","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Innsbruck","place":["Innsbruck, Austria"]},{"name":"VASCage - Center for Clinical Stroke Research","place":["Innsbruck, Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregor","family":"Broessner","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Innsbruck","place":["Innsbruck, Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.3390\/brainsci13081217","article-title":"The potential of gut microbiota in prediction of stroke-associated pneumonia","volume":"13","author":"Li","year":"2023","journal-title":"Brain Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1186\/s12890-025-03750-6","article-title":"Procalcitonin and biomarkers for stroke-associated pneumonia: a systematic review and meta-analysis","volume":"25","author":"Wang","year":"2025","journal-title":"BMC Pulm Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fcimb.2021.715475","article-title":"Dysbiosis of gut microbiota is an independent risk factor of stroke-associated pneumonia: a Chinese pilot study","volume":"11","author":"Xia","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"3161","DOI":"10.1016\/j.jtha.2024.06.028","article-title":"Elevated lipopolysaccharide level is largely driven by time since symptom onset in acute ischemic stroke: the impact on clinical outcomes","volume":"22","author":"B\u0142a\u017c","year":"2024","journal-title":"J Thromb Haemost."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fncel.2025.1557746","article-title":"Intestinal injury and changes of the gut microbiota after ischemic stroke","volume":"19","author":"Shen","year":"2025","journal-title":"Front Cell Neurosci"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1287928","DOI":"10.3389\/fneur.2023.1287928","article-title":"Effect of TMAO on the incidence and prognosis of cerebral infarction: a systematic review and meta-analysis","volume":"14","author":"Wang","year":"2024","journal-title":"Front Neurol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1491880","DOI":"10.3389\/fimmu.2025.1491880","article-title":"Antibodies against neuronal surface antigens in acute stroke: a systematic review and meta-analysis","volume":"16","author":"Paolucci","year":"2025","journal-title":"Front Immunol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"46","DOI":"10.3390\/epidemiologia6030046","article-title":"Prevalence and factors associated with infections after acute ischemic stroke: a single-center retrospective study over five years","volume":"6","author":"Rinawati","year":"2025","journal-title":"Epidemiologia."},{"key":"B9","doi-asserted-by":"publisher","first-page":"2076","DOI":"10.3390\/medicina60122076","article-title":"The role of complete blood count-derived inflammatory biomarkers as predictors of infection after acute ischemic stroke: a single-center retrospective study","volume":"60","author":"Rinawati","year":"2024","journal-title":"Medicina."},{"key":"B10","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1186\/s12883-024-03968-7","article-title":"systematic review and meta-analysis show a decreasing prevalence of post-stroke infections","volume":"24","author":"Awere-Duodu","year":"2024","journal-title":"BMC Neurol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fneur.2020.590480","article-title":"RANK\/RANKL\/OPG signaling in the brain: a systematic review of the literature","volume":"11","author":"Glasnovi\u0107","year":"2020","journal-title":"Front Neurol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-323263","article-title":"Rapid gut dysbiosis induced by stroke exacerbates brain infarction in turn","author":"Xu","year":"2021","journal-title":"Gut"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2023.1141387","article-title":"The gastrointestinal-brain-microbiota axis: a promising therapeutic target for ischemic stroke","volume":"14","author":"Wei","year":"2023","journal-title":"Front Immunol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/biomedicines12122781","article-title":"Gut microbiota, bacterial translocation, and stroke: current knowledge and future directions","volume":"12","author":"Granados-Martinez","year":"2024","journal-title":"Biomedicines."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fnins.2023.1081347","article-title":"Gut-brain axis: mechanisms and potential therapeutic strategies for ischemic stroke through immune functions","volume":"17","author":"Zhou","year":"2023","journal-title":"ront Neurosci"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2025.1547365","article-title":"Post-stroke depression: exploring gut microbiota-mediated barrier dysfunction through immune regulation","volume":"16","author":"Jiang","year":"2025","journal-title":"Front Immunol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1007\/s12975-023-01151-7","article-title":"The involvement of immune cells between ischemic stroke and gut microbiota","volume":"15","author":"Pu","year":"2024","journal-title":"Transl Stroke Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"6176","DOI":"10.1007\/s12035-023-03473-x","article-title":"Microbiota metabolites and immune regulation affect ischemic stroke occurrence, development, and prognosis","volume":"60","author":"Wang","year":"2023","journal-title":"Mol Neurobiol."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1702025\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T04:33:53Z","timestamp":1777350833000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1702025\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,28]]},"references-count":18,"alternative-id":["10.3389\/fmed.2025.1702025"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1702025","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,28]]},"article-number":"1702025"}}